It is known that a patient with renal dysfunction gradually loses a capability to excrete the body's phosphorus into urine due to a decline in renal functions associated with a deterioration of the renal lesion and results in hyperphosphatemia. In patients who suffer from the condition of hyperphosphatemia for an extended period, phosphorus accumulated in the body induces various hazards such as a decrease in serum calcium, and thus medical treatment of hyperphosphatemia was indispensable for the patients.
For the treatment of hyperphosphatemia, a therapy by oral administration of a phosphorus adsorbent has been practiced as well as the dietetic therapy. The therapy by oral administration of a phosphorus adsorbent is based on a function of the phosphorus adsorbent to adsorb and trap phosphate ions present in food ingested by the patient, thus suppressing intake and accumulation of phosphorus in the body and consequently reducing phosphorus concentration in blood. Currently, three kinds of medicines, aluminum preparations, calcium preparations and magnesium preparations, are mainly used as the oral phosphorus adsorbent. But since the medicines are necessarily administrated for a prolonged term for those patients with renal failure, the aluminum preparations containing aluminum hydroxide raise a problem of adverse reactions such as aluminum encephalopathy and aluminum osteopathy induced by the uptake of aluminum into the patient body. Additionally, the calcium preparations (calcium carbonate, calcium acetate) have the similar problem since they have lower phosphorus adsorption capacities compared to the aluminum preparations, demanding an increased administration of the medicine and consequently resulting in an uptake of more calcium possibly leading to hypercalcemia. Moreover, the magnesium preparations (magnesium carbonate) have a problem of hypermagnesemia, as with the calcium preparations.
In view of the problems associated with the conventional oral phosphorus adsorbents for medicine, recently, methods to use an anion exchange resin as the phosphorus adsorbent have been studied. For example, Japanese PCT International Publication No. 9-504782 (WO95/05184) discloses that an anion exchange resin of polyallylamine hydrochloride crosslinked with epichlorohydrin can be used as a medicinal phosphoric acid adsorbent. Additionally, in Japanese Unexamined Patent Publication No. 9-295941 was disclosed that 2-methylimidazole-epichlorohydrin copolymer, cholestyramine and the like that were used as bile acid adsorbents can also be used as medicinal phosphorus adsorbents, and in Japanese PCT International Publication No. 8-506846 (WO96/25440) that an anion exchange resin having guanitidyl (sic) groups may adsorb phosphoric acid.
Although these anion exchange resins exhibit sufficient adsorption capacities with respect to phosphate ion, there were some resins that should be administered in a greater amount to raise the therapeutic effect. Additionally, according to a survey in the U.S., about 25% of the renal failure patients were concurrently suffering from hyperlipemia, while the remaining 75% patients were not required to decrease the blood cholesterol level. But among the conventional medicinal phosphorus adsorbents, there were some that adsorb not only phosphoric acid, but also organic acids including raw materials of cholesterol such as bile acids (e.g., glycocholic acid), and consequently induce the hazard of a decrease in the blood cholesterol level. Therefore, there was a need to raise both the phosphoric acid adsorption capacity and the phosphoric acid selectivity.
Thereupon, objects of the present invention are to find a crosslinked anion exchange resin that is excellent both in the phosphorus adsorption capacity and the selectivity to phosphorus, and to provide a phosphorus adsorbent comprising the crosslinked anion exchange resin or the salt thereof, by studying kinds of anion exchange resin and effects of crosslinking with crosslinking agents.